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Correlation Study between in Vitro Release and in Vivo Absorption of Venetoclax

??OBJECTIVE To investigate the in-vitro release behavior of venetoclax preparations, the pharmacokinetic processes and the correlations between in-vitro release and in-vivo absorption of venetoclax in Beagle dogs. METHODS The dissolution curves of venetoclax preparations in different dissolution media were studied. HPLC method was established for the determination of venetoclax in Beagle dogs, and the pharmacokinetics were studied for commercial venetoclax tablets in Beagle dogs under fed and fasted states.The IVIVC study was carried out by linear regression of cumulative in-vitro drug release and in-vivo absorption accumulation percentage data. RESULTS The in-vitro release behavior among venetoclax formulation in 4 dissolution media were significant difference. The simple, accurate and rapid analysis method for venetoclax blood samples was established. The fed group and the fasted group AUC_0???? were (32.38??5.87) and (27.70??6.32) mg??h??L^-1, the concentration of peak were (4.04??0.78) and (3.72 ??0.69) ??g??mL^-1, the peak time were (6.01??1.04) and (4.27??0.92) h, respectively, and there was obvious difference (P<0.05) in AUC_0???? and the peak time between two group. Percentage of in-vivo absorption was in good agreement with in-vitro release in pH 6.8 0.2%SDS media. CONCLUSION The study shows that food could improve the bioavailability of venetoclax formulation; 0.2%SDS pH 6.8 media (paddle, 75 r??min^-1) is the in-vivo release of venetoclax associated with the in-vitro release condition.